Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Irreversible inactivation of striatal D2 dopamine (DA) autoreceptors with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) or inactivation of striatal guanine nucleotide binding proteins (G proteins) with pertussis toxin (PT) shifted the dose-response curve for N-n-propylnorapomorphine (NPA)-mediated inhibition of gamma-butyrolactone (GBL)-induced elevation of L-3,4-dihydroxyphenylalanine (L-DOPA) to the right, with a decrease in the maximum response. For the partial agonist (+)-3-(3-hydroxyphenyl)-N-n-propylpiperidine [(+)-3-PPP], in contrast, there was little shift in the ED50, after inactivation of either D2 receptors or G proteins. Completely analogous effects were found at the somatodendritic 5-HT1A autoreceptor in the raphe nuclei, mediating inhibition of the synthesis of serotonin (5-HT); the full agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the partial agonist, buspirone were utilized to inhibit the synthesis of 5-HT, as measured by changes in levels of L-5-hydroxytryptophan (5-HTP). Additionally, in both systems, combined treatment with pertussis toxin, followed by EEDQ, reduced the maximum effect, when compared to either agent alone but had little further effect on the ED50. In systems exhibiting a large receptor reserve for agonists, such as those described above, the same pattern of response seen after inactivation of receptors or G proteins may reflect the operation of a common mechanism underlying the phenomenon of receptor reserve.
 ...
PMID:The effects of pertussis toxin on dopamine D2 and serotonin 5-HT1A autoreceptor-mediated inhibition of neurotransmitter synthesis: relationship to receptor reserve. 135 48

Agents that elevate intracellular cyclic AMP (cAMP) have been found to enhance the synaptic discharge of norepinephrine (NE) from sympathetic nerve terminals in the rabbit iris-ciliary body and other peripheral tissues. We explored the hypothesis that prejunctional alpha 2-adrenergic receptors that mediate feedback inhibition of NE release may be coupled to adenylyl cyclase inhibition. To indirectly monitor cAMP changes in sympathetic axon terminals, we analyzed the cAMP-mediated activation of tyrosine hydroxylase, a sympathetic marker protein that undergoes acute phosphorylation and activation by cAMP-dependent protein kinase A. Tyrosine hydroxylase activity was assayed in situ by incubation of rabbit iris-ciliary body tissue segments in buffered Krebs-Ringer solution containing the substrate tyrosine (100 microM) and the DOPA decarboxylase inhibitor brocresine (30 microM). Intraneuronal DOPA accumulation was quantified by HPLC with electrochemical detection. Tyrosine hydroxylase activity was increased approximately 2 fold by incubation with forskolin (10 microM) plus IBMX (0.5 mM) or with 8-Bromo-cAMP (3 mM). Simultaneous addition of the alpha 2-adrenergic agonist clonidine (1 microM) attenuated the response to forskolin/IBMX, but had no effect on the response to 8-Br-cAMP. Clonidine-mediated inhibition of the forskolin/IBMX response was abolished by treatment of tissues with N-ethylmaleimide (NEM), an alkylating agent that inactivates pertussis toxin-sensitive G proteins (Gi) that couple receptors to adenylyl cyclase inhibition. These findings suggest that prejunctional alpha 2-adrenoceptors in the rabbit iris-ciliary body are negatively coupled to adenylyl cyclase. This mechanism may contribute to autofeedback regulation of NE biosynthesis and release.
 ...
PMID:Prejunctional alpha 2-adrenoceptors and adenylyl cyclase regulation in the rabbit iris-ciliary body. 771 5

The involvement of dopamine (DA) receptor subtypes in regulation of renal phosphate transport by DA, either exogenous or locally synthesized from L-dihydroxyphenylalanine (L-dopa) was evaluated in opossum kidney (OK) cells with proximal tubular phenotype. DA synthesis from L-dopa by OK cells was abolished by carbidopa and benserazide, two dissimilar inhibitors of aromatic L-amino acid decarboxylase. L-Dopa stimulated cyclic AMP generation and inhibited Na-dependent Pi uptake, and these effects were abolished by carbidopa and benserazide. The effects of L-dopa or DA on cyclic AMP generation and on Na-Pi co-transport were mimicked by SKF 38393, a DA1 receptor agonist, and were potentiated by S-sulpiride, a DA2 receptor antagonist. Bromocriptine, a DA2 receptor agonist, blunted in a pertussis toxin-dependent manner parathyroid hormone (PTH)-induced cyclic AMP generation and inhibition of Pi uptake. In contrast with PTH, neither L-dopa nor DA affected significantly the cytosolic calcium concentration. These results support the involvement of DA1 and DA2 receptors, positively and negatively coupled into adenylate cyclase respectively, in modulation of renal phosphate transport.
 ...
PMID:Locally formed dopamine modulates renal Na-Pi co-transport through DA1 and DA2 receptors. 852 52

The effects of pertussis toxin (PTX) pretreatment on basal and morphine-affected changes of tuberoinfundibular dopaminergic (TIDA) neuron activity and serum prolactin level were tested in this study. Adult female Sprague-Dawley rats, ovariectomized and treated with a long-acting estrogen (polyestradiol phosphate, 0.1 mg/rat, s.c.), were used. The activity of TIDA neurons was determined by measuring the turnover rate of dopamine (DA), and the concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) or 3,4-dihydroxyphenylalanine (DOPA) in the median eminence. Acute (30-90 min) treatment of PTX had no significant effect on any of the parameters measured. Prolonged (24 h) treatment of PTX significantly reduced morphine's inhibitory effect on TIDA neuron activity (using DOPA, but not DOPAC as the index), and stimulatory effect on PRL release. Basal TIDA neuron activity as determined by median eminence DOPAC concentration, DOPA accumulation, or DA rate constant was not significantly altered by PTX. Median eminence DA level, however, was significantly reduced. These results suggest that a pertussis toxin-sensitive GTP-binding protein may be responsible for the maintenance of TIDA neurons, and for mediation of the inhibitory effect of morphine on TIDA neuron activity, and in turn, the stimulation of prolactin secretion.
 ...
PMID:Prolonged pertussis toxin treatment affects morphine's action on tuberoinfundibular dopaminergic neuron activity and on prolactin secretion. 884 96

In PC12 rat pheochromocytoma cells differentiated with nerve growth factor (NGF), neuropeptide Y inhibited depolarization-stimulated catecholamine synthesis as determined by in situ measurement of 3,4-dihydroxyphenylalanine (DOPA) production in the presence of the decarboxylase inhibitor m-hydroxybenzylhydrazine (NSD-1015). The inhibition by neuropeptide Y was concentration-dependent and was prevented by pretreatment with pertussis toxin, suggesting the involvement of a GTP-binding protein of the Gi or Go subtype. The neuropeptide Y analog [Leu31,Pro34]neuropeptide Y also caused inhibition of DOPA production, but was less potent than neuropeptide Y itself, while peptide YY and neuropeptide Y-(13-36) had no significant effect. This pattern is most consistent with the involvement of the neuropeptide Y Y3 receptor subtype. In PC12 cells differentiated with dexamethasone, neuropeptide Y also caused a concentration-dependent inhibition of DOPA production, while peptide YY was again without effect. Neuropeptide Y had no effect on DOPA production in undifferentiated PC12 cells. These results indicate that neuropeptide Y can modulate catecholamine synthesis in addition to its modulatory effects on catecholamine release.
 ...
PMID:Neuropeptide Y inhibits depolarization-stimulated catecholamine synthesis in rat pheochromocytoma cells. 899 1

We have earlier shown that the renal dopaminergic system failed to respond to high salt (HS) intake in old (24-month-old) Fisher 344 rats (Hypertension 1999;34:666-672). In the present study, intestinal Na+,K+-ATPase activity and intestinal dopaminergic tonus were evaluated in adult and old Fischer 344 rats during normal salt (NS) and HS intake. Basal intestinal Na+,K+-ATPase activity (nmol Pi/mg protein/min) in adult rats (142+/-6) was higher than in old Fischer 344 rats (105+/-7). HS intake reduced intestinal Na+,K+-ATPase activity by 20% (P<0.05) in adult, but not in old rats. Dopamine (1 microM) failed to inhibit intestinal Na+,K+-ATPase activity in both adult and old Fischer 344 rats (NS and HS diets). In adult animals, co-incubation of pertussis toxin with dopamine (1 microM) produced a significant inhibitory effect in the intestinal Na+,K+-ATPase activity. L-DOPA and dopamine tissue levels in the intestinal mucosa of adult rats were higher (45+/-9 and 38+/-4 pmol/g) than those in old rats (27+/-9 and 14+/-1 pmol/g). HS diet did not change L-DOPA and DA levels in both adult and old rats. DA/L-DOPA tissue ratios, an indirect measure of dopamine synthesis, were higher in old (1.1+/-0.2) than in adult rats (0.6+/-0.1). Aromatic L-amino acid decarboxylase (AADC) activity in the intestinal mucosa of old rats was higher than in adult rats. HS diet increased the AADC activity in adult rats, but not in old rats. It is concluded that intestinal dopaminergic tonus in old Fisher 344 rats is higher than in adult rats and is accompanied by lower basal intestinal Na+,K+-ATPase activity. In old rats, HS diet failed to alter the intestinal dopaminergic tonus or Na+,K+-ATPase activity, whereas in adult rats increases in AADC activity were accompanied by decreases in Na+,K+-ATPase activity. The association between salt intake, increased dopamine formation and inhibition of Na+,K+-ATPase at the intestinal level was not as straightforward as that described in renal tissues.
 ...
PMID:Salt intake and intestinal dopaminergic activity in adult and old Fischer 344 rats. 1158 11